Periodontitis is an infectious disease caused by the formation of bacterial plaque on teeth. Porphyromonas gingivalis (P. gingivalis) is one of these bacteria, and has been used in many experimental models of periodontitis to replicate the inflammation and bone resorption seen in clinical cases. It is well understood that stress exacerbates the inflammation and bone resorption associated with chronic periodontitis, and that the primary cause of the tissue destruction and tooth loss is the prolonged inflammation and presence of proinflammatory cytokines such as Interleukin-12 (IL-12). Furthermore, neuropeptides, such as the highly abundant neuropeptide Y (NPY), have been found at the site of infected periodontal tissue and may play a role in modulating norepinephrine and subsequent inflammation. Norepinephrine is thought to promote inflammation by modulating cytokine release and is thought to be involved in immune cell trafficking. Using a murine model of social stress along with transgenic mouse technology and antagonists, we will examine the relationship of IL-12, NPY, and norepinephrine in the absence of infection in order to elucidate the modulatory mechanisms in vivo. Additionally, we will manipulate IL-12, NPY, and norepinephrine in a mouse model of stress-exacerbated chronic periodontitis to determine whether blocking any of these mediators can resolve inflammation and [bone resorption] associated with the deleterious effects of periodontitis. Exploring the specific mechanisms of periodontal inflammation and [bone resorption] will aid in identifying novel therapeutic targets that will improve the clinical outcomes of chronic periodontitis.